Our laboratory is interested in the biology of p53 with a focus on its regulation of metabolism and how this can impact cancer and cardiovascular biology. To this end, we are studying Li-Fraumeni syndrome (LFS), an early onset cancer disorder caused by germline mutations in the TP53 gene, using both mouse models and translational studies involving LFS patients. Our investigations to date have yielded insights that may be useful for developing new strategies for preventing cancer and maintaining cardiovascular health. We are in the process of planning a larger translational study examining the use of metformin for chemoprevention in LFS patients as a collaborative project between NIH intramural and extramural investigators. We have also created two new LFS mouse models based on human mutations to understand their biology.